Development of a Personalized Decision Aid for Breast Cancer Risk Reduction and Management

Background: Breast cancer risk reduction has the potential to decrease the incidence of the disease, yet remains underused. We report on the development a web-based tool that provides automated risk assessment and personalized decision support designed for collaborative use between patients and clinicians. Methods: Under Institutional Review Board approval, we evaluated the decision tool through a patient focus group, usability testing, and provider interviews (including breast specialists, primary care physicians, genetic counselors). This included demonstrations and data collection at two scientific conferences (2009 International Shared Decision Making Conference, 2009 San Antonio Breast Cancer Symposium). Results: Overall, the evaluations were favorable. The patient focus group evaluations and usability testing (N = 34) provided qualitative feedback about format and design; 88% of these participants found the tool useful and 94% found it easy to use. 91% of the providers (N = 23) indicated that they would use the tool in their clinical setting. Conclusion: BreastHealthDecisions.org represents a new approach to breast cancer prevention care and a framework for high quality preventive healthcare. The ability to integrate risk assessment and decision support in real time will allow for informed, value-driven, and patient-centered breast cancer prevention decisions. The tool is being further evaluated in the clinical setting

Reducing false-positive biopsies: a pilot study to reduce benign biopsy rates for BI-RADS 4A/B assessments through testing risk stratification and new thresholds for intervention

The aim of this study is to evaluate Breast Imaging Reporting and Data Systems (BI-RADS) 4A/B subcategory risk estimates for ductal carcinoma in situ (DCIS) and invasive cancer (IC), determining whether changing the proposed cutoffs to a higher biopsy threshold could safely increase cancer-to-biopsy yields while minimizing false-positive biopsies. A prospective clinical trial was performed to evaluate BI-RADS 4 lesions from women seen in clinic between January 2006 and March 2007. An experienced radiologist prospectively estimated a percent risk-estimate for DCIS and IC. Truth was determined by histopathology or 4-year follow-up negative for malignancy. Risk estimates were used to generate receiver-operating characteristic (ROC) curves. Biopsy rates, cancer-to-biopsy yields, and type of malignancies missed were then calculated across postulated risk thresholds. A total of 124 breast lesions were evaluated from 213 women. An experienced radiologist gave highly accurate risk estimates for IC, DCIS alone, or the combination with an area under ROC curve of 0.91 (95 % CI 0.84–0.99) (p < 0.001), 0.81 (95 % CI 0.69–0.93) (p = 0.011), and 0.89 (95 % CI 0.83–0.95) (p < 0.001), respectively. The cancer-to-biopsy yield was 30 %. Three hypothetical thresholds for intervention were analyzed: (1) DCIS or IC ≥ 10 %; (2) DCIS ≥ 50 % or IC ≥ 10 %; and (3) IC ≥ 10 %, which translated to 22, 48, and 56 % of biopsies avoided; cancer-to-biopsy yields of 36, 47, and 46 %; and associated chance of missing an IC of 0, 1, and 2 %, respectively. Expert radiologists estimate risk of IC and DCIS with a high degree of accuracy. Increasing the cut off point for recommending biopsy, substituting with a short-term follow-up protocol with biopsy if any change, may safely reduce the number of false-positive biopsies

Mammographic screening detects low-risk tumor biology breast cancers.

Overdiagnosis of breast cancer, i.e. the detection of slow-growing tumors that would never have caused symptoms or death, became more prevalent with the implementation of population-based screening. Only rough estimates have been made of the proportion of patients that are overdiagnosed and identification of those patients is difficult. Therefore, the aim of this study is to evaluate whether tumor biology can help identify patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Furthermore, we wish to evaluate the impact of the transition from film-screen mammography (FSM) to the more sensitive full-field digital mammography (FFDM) on the biology of the tumors detected by each screening-modality. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007-2011, who participated in the national screening program (biennial screening ages 50-75) were included (n = 1,165). We calculated the proportions of high-, low- and among those the ultralow-risk tumors according to the 70-gene signature for patients with screen-detected (n = 775) and interval (n = 390) cancers for FSM and FFDM. Screen-detected cancers had significantly more often a low-risk tumor biology (68 %) of which 54 % even an ultralow-risk compared to interval cancers (53 % low-, of which 45 % ultralow-risk (p = 0.001) with an OR of 2.33 (p &lt; 0.0001; 95 % CI 1.73-3.15). FFDM detected significantly more high-risk tumors (35 %) compared to FSM (27 %) (p = 0.011). Aside from favorable clinico-pathological factors, screen-detected cancers were also more likely to have a biologically low-risk or even ultralow-risk tumor. Especially for patients with screen-detected cancers the use of tools, such as the 70-gene signature, to differentiate breast cancers by risk of recurrence may minimize overtreatment. The recent transition in screening-modalities led to an increase in the detection of biologically high-risk cancers using FFDM

Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

Markers for the identification of late breast cancer recurrence

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Rapid Detection Of Brca1/2 Recurrent Mutations In Chinese Breast And Ovarian Cancer Patients With Multiplex Snapshot Genotyping Panels

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